Prostanoids and hypothermic renal preservation injury.
The effect of 48 hours of hypothermic renal ischemia utilizing Euro-Collins flush and short term reperfusion on renal prostaglandin synthesis was studied in dogs. Hypothermic ischemia followed by 60 minutes of reperfusion in-vivo resulted in significant elevations in renal Thromboxane B2 (TXB2) production in the outer cortex, inner cortex, and medulla, relative to non-ischemic kidneys. Prostaglandin E2 (PGE2) and 6-keto Prostaglandin F1 alpha (6-K PGF1 alpha) production were not significantly affected by ischemia and reperfusion. Enhanced TXB2 production was not seen with ischemia alone (without reperfusion) or with reperfusion with O2 saturated buffer, indicating a blood born source or stimuli. Early postreperfusion renal blood flow after hypothermic ischemia followed a biphasic pattern; blood flow increased for the first 10 minutes of reperfusion to achieve normal values, and then steadily declined over the next 20 minutes. This pattern was not altered by the cyclooxygenase inhibitors Idomethacin (5 mg/kg, P.O.) or Mefenamic acid (10 mg/kg, I.V.). Administration of the TXA2 synthesis inhibitor CGS-12970 (3 mg/kg, I.V.) or the TXA2/endoperoxide receptor antagonist SQ-29548 (80 micrograms/min, I.A.) significantly increased renal blood flow during reperfusion but neither agent altered the basic time dependent pattern observed in the control group. These data indicate that 48 hours of hypothermic renal ischemia results in dramatic changes in intrarenal TXA2 synthesis at the time of reperfusion. Enhanced TXA2 production is not dependent on reoxygenation per se, but rather requires reperfusion with blood suggesting a circulatory source.(ABSTRACT TRUNCATED AT 250 WORDS)
Mangino
M J
MJ
Department of Surgery, Washington University School of Medicine, St. Louis, Missouri 63110.
Jendrisak
M D
MD
Murphy
M K
MK
Halstead
M
M
Anderson
C B
CB
D000818:Animals; D019086:Bridged Bicyclo Compounds, Heterocyclic; D003080:Cold Temperature; D004285:Dogs; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines / Q000494:pharmacology; D066298:In Vitro Techniques; D007668:Kidney / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology; D009926:Organ Preservation; D011453:Prostaglandins / Q000096:biosynthesis / Q000502:physiology*; D011725:Pyridines / Q000494:pharmacology; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology; D015427:Reperfusion Injury / Q000503:physiopathology*; D013931:Thromboxanes / Q000037:antagonists & inhibitors / Q000096:biosynthesis
D019086:Bridged Bicyclo Compounds, Heterocyclic; D005231:Fatty Acids, Unsaturated; D006834:Hydrazines; D011453:Prostaglandins; D011725:Pyridines; D013931:Thromboxanes; C049113:3-methyl-2-(3-pyridyl)-1-indoleoctanoic acid; C045749:SQ 29548